Effect of intranasal sufentanil on acute post-traumatic pain in the emergency department: a randomised controlled trial.

BACKGROUND: Intranasal sufentanil is a potent opioid which can be used in patients with traumatic injuries presenting to the ED. Although previous studies have demonstrated the superiority of intranasal sufentanil over intravenous morphine in terms of pain relief, its clinical superiority in patients with traumatic injuries receiving adequate multimodal analgesia with acetaminophen and non-steroidal anti-inflammatory drugs is uncertain. We compared pain relief offered by intranasal sufentanil with that offered by oral and intravenous opioids in patients with acute traumatic injuries also receiving a specified regimen of non-opioid treatment. METHODS: In this single-centre, open-label, parallel-group, randomised controlled superiority trial conducted between January 2020 and February 2022, trauma patients presenting to the ED with a pain score of ≥7 on a visual analogue scale (VAS) were randomised to receive either intranasal sufentanil or other oral/intravenous opioids alongside oral/intravenous acetaminophen and non-steroidal anti-inflammatory drugs. The primary outcome was reduction in VAS score 15-20 min after randomisation. RESULTS: An intention-to-treat analysis included 170 out of 205 patients screened for inclusion. The intranasal sufentanil group (83 patients) showed a significantly greater reduction in pain when compared with the oral/intravenous opioid group (87 patients) 15-20 min after randomisation (reduction in VAS score 3.0 (IQR 1.7-5.0) vs 1.5 (IQR 0.9-3.0); p<0.001). Similarly, a greater reduction in pain was observed in the intranasal sufentanil group 60 min after randomisation (5.0 (IQR 3.0-7.0) vs 3.0 (IQR 2.0-5.3); p<0.001). However, side effects were more frequent in the intervention group (71.1% vs 23%; p<0.001). CONCLUSIONS: Intranasal sufentanil was associated with more effective pain relief than oral/intravenous opioids in patients with traumatic injuries treated with coanalgesia. Intranasal sufentanil could be considered for the management of pain in patients with traumatic injuries associated with severe pain. TRIAL REGISTRATION NUMBER: NCT04137198.

Severe vitamin D deficiency in patients admitted to the emergency department with severe sepsis is associated with an increased 90-day mortality.

BACKGROUND: The role of vitamin D in the response to infection has been increasingly acknowledged. However, the influence of severe vitamin D deficiency on the outcome of patients admitted for severe sepsis is unknown. Hence, this study aimed to investigate the association between severe vitamin D deficiency and sepsis-related outcomes in patients presenting to the ED. METHODS: This single centre prospective study included patients presenting to the ED with severe sepsis from April 2014 until December 2017. 25-Hydroxy vitamin D (25(OH)D) was measured in a blood sample drawn within 24 hours of admission to the ED, and severe vitamin D deficiency was defined as 25(OH)D <12 ng/mL. 90-day mortality was compared between patients with and without severe vitamin D deficiency by a multivariable analysis adjusting for confounders and according to a Kaplan-Meier survival analysis. RESULTS: 263 patients were initially screened and 164 patients with severe sepsis were included in this study, 18% of whom had septic shock. Severe vitamin D deficiency was present in 46% of patients. The overall 90-day mortality rate was 26.2% and the median length of stay was 14 days. In a logistic regression accounting for sepsis severity and age-adjusted comorbidities, severe vitamin D deficiency was associated with increased mortality (OR=2.69 (95% CI 1.03 to 7.00), p=0.043), and lower chances of hospital discharge (sub-HR=0.66 (95% CI 0.44 to 0.98)). In the subgroup of patients admitted to the intensive care unit, severe vitamin D deficiency was associated with an increased 28-day adjusted mortality (HR=3.06 (95% CI 1.05 to 8.94), p=0.04) and lower chances of discharge (sub-HR=0.51 (95% CI 0.32 to 0.81)). CONCLUSIONS: Severe vitamin D deficiency at ED admission is associated with higher mortality and longer hospital stay in patients with severe sepsis.

Clinical impact of the rapid molecular detection of RSV and influenza A and B viruses in the emergency department.

INTRODUCTION: Using respiratory virus rapid diagnostic tests in the emergency department could allow better and faster clinical management. Point-of-care PCR instruments now provide results in less than 30 minutes. The objective of this study was to assess the impact of the use of a rapid molecular diagnostic test, the cobas® Influenza A/B & RSV Assay, during the clinical management of emergency department patients. METHODS: Patients (adults and children) requiring admission or suffering from an underlying condition at risk of respiratory complications were prospectively recruited in the emergency department of four hospitals in the Brussels region. Physicians' intentions regarding admission, isolation, antibiotic, and antiviral use were collected before and after performing the rapid molecular test. Additionally, a comparison of the analytical performance of this test against antigen rapid tests and viral culture was performed as well as a time-to-result evaluation. RESULTS: Among the 293 patients recruited, 90 had a positive PCR, whereas 44 had a positive antigen test. PCR yielded a sensitivity of 100% for all targets. Antigen tests yielded sensitivities ranging from 66.7% for influenza B to 83.3% for respiratory syncytial virus (RSV). The use of PCR allowed a decrease in the overall need for isolation and treatment by limiting the isolation of negative patients and antibiotic use for positive patients. Meanwhile, antiviral treatments better targeted patients with a positive influenza PCR. CONCLUSION: The use of a rapid influenza and RSV molecular test improves the clinical management of patients admitted to the emergency department by providing a fast and reliable result. Their additional cost compared to antigen tests should be balanced with the benefit of their analytical performance, leading to efficient reductions in the need for isolation and antibiotic use.

Diagnostic Accuracy of Procalcitonin upon Emergency Department Admission during SARS-CoV-2 Pandemic.

INTRODUCTION: Procalcitonin is a marker for bacterial diseases and has been used to guide antibiotic prescription. Procalcitonin accuracy, measured at admission, in patients with community-acquired pneumonia (CAP), is unknown in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. OBJECTIVES: To evaluate the diagnostic accuracy of procalcitonin to assess the need for antibiotic treatment in patients with CAP presenting to the emergency department during the SARS-CoV-2 pandemic. METHODS: We performed a real-world diagnostic retrospective accuracy study of procalcitonin in patients admitted to the emergency department. Measures of diagnostic accuracy were calculated based on procalcitonin results compared to the reference standard of combined microbiological and radiological analysis. Sensitivity, specificity, positive and negative predictive values, and area under (AUC) the receiver-operating characteristic (ROC) curve were calculated in two analyses: first assessing procalcitonin ability to differentiate microbiologically proven bacteria from viral CAP and then clinically diagnosed bacterial CAP from viral CAP. RESULTS: When using a procalcitonin threshold of 0.5 ng/mL to identify bacterial etiology within patients with CAP, we observed sensitivity and specificity of 50% and 64.1%, and 43% and 82.6%, respectively, in the two analyses. The positive and negative predictive values of a procalcitonin threshold of 0.5 ng/mL to identify patients for whom antibiotics should be advised were 46.4% and 79.7%, and 48.9% and 79% in the two analyses, respectively. The AUC for the two analyses was 0.60 (95% confidence interval [CI] 0.52-0.68) and 0.62 (95% CI, 0.55-0.69). CONCLUSIONS: Procalcitonin measured upon admission during the SARS-CoV-2 pandemic should not guide antibiotic treatment in patients with CAP.

Risk assessment, consequences, and epidemiology of electric scooter accidents admitted to an emergency department: a prospective observational study.

PURPOSE: This study aimed to describe the demographic and clinical characteristics of individuals involved in electric scooter (E-scooter) accidents and the factors associated with these incidents. METHODS: We conducted a prospective observational study of individuals involved in E-scooter accidents admitted to the emergency department of Saint-Pierre Hospital. The highest abbreviated injury score above or equal to two classified the injury as significant. Injuries during working hours were compared to those during off-working hours. RESULTS: During the study period from June 1, 2019, to June 30, 2020, 170 individuals were admitted to the emergency department following an E-scooter accident. In 73.5% of the accidents, rented E-scooters were involved. Of the patients, 68.2% were male, 6.4% wore helmets, and 30% were under the influence of alcohol. Upper limb and cranial injuries were more frequently severe (abbreviated injury score ≥ 2) than other injuries (p < 0.05). Accidents during off-working hours were significantly related to alcohol consumption (p < 0.001), non-usage of helmets (p < 0.01), head and neck injuries (p < 0.01), and rented E-scooters (p < 0.01). Alcohol consumption was itself associated with the non-usage of helmets (p < 0.05) and major head and neck injuries (p < 0.001). CONCLUSION: Given the increasing popularity of E-scooters as an alternative mode of transportation, our study can inform public policy on patterns of injuries associated with E-scooter utilization for future injury prevention policies. Using helmets, avoiding alcohol consumption, and regulating use at night can improve outcomes in E-scooter accidents. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04778332.

Impact of treatment delays on outcome of acute testicular torsion: a 15-year retrospective study.

INTRODUCTION: Preservation of the testicle is directly associated with the duration of torsion. The aim in this retrospective study was to identify factors that influence pre-and in-hospital times and measure the extent to which these times affect testicle survival. PATIENTS AND METHODS: A retrospective review of 116 patients who underwent exploration for testicular torsion between 2000 and 2015. Patients were divided into orchiectomy and salvaged testicle groups. Times in patient management and clinical features were compared with Mann-Whitney, chi-squared, and Fisher exact tests. Multivariate logistical regression was used to identify independent factors associated with orchiectomy. RESULTS: The median prehospital time of 48 h (15.4-138 h) in the orchiectomy group was longer than the 2.4 h (1.6 h-5.2h) in the salvaged group. Patients examined by a general practitioner (GP) prior to presenting at hospital had a median prehospital time of 48 h, compared to 3 h for patients not examined before presentation at hospital. In-hospital times between admission and operation room, as well as times between ultrasonography and operation room, were also longer in the orchiectomy group. Previous GP consultation (OR = 27.26, 95% CI 2.32-320.59, p = .009), prehospital time (OR = 1.04, 95% CI 1.01-1.07, p = .003) and nausea (OR = 9.25, 95% IC 1.33-64.52, p = .025) were independent predictive factors associated with orchiectomy. CONCLUSION: Prehospital time was a determining factor in orchiectomy. For each extra hour of prehospital delay, the risk of orchiectomy increased by 4%. The rate of orchiectomy was higher among patients who first consulted a GP.

Fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) post Ad26.COV2.S: first documented case outside US.

PURPOSE: We reported the first described post Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine-induced immune thrombocytopenia (VITT) case outside US.  CASE DESCRIPTION: CA young woman without any medical history presented association of deep vein thrombosis and thrombocytopenia at day 10 after vaccine injection. The patient was treated with low-molecular weight heparin at a first medical institution. Twelve days post Ad26.COV2.S vaccination, the patient was admitted at our hospital for neurological deterioration and right hemiplegia. Medical imaging using MRI showed thrombosis of the major anterior part of the sagittal superior sinus with bilateral intraparenchymal hemorrhagic complications. Screening tests for antibodies against platelet factor 4 (PF4)-heparin by rapid lateral flow immunoassay and chemiluminescence techniques were negative. Platelet activation test using heparin-induced multiple electrode aggregometry confirmed the initial clinical hypothesis. Despite immediate treatment with intravenous immunoglobulin, dexamethasone, danaparoid and attempted neurosurgery the patient evolved toward brain death. CONCLUSION: Even though it is an extremely rare complication of vaccination physicians should maintain a high index of suspicion of VITT in patients who received an adenovirus-vector-based SARS-CoV-2 vaccine within the last 30 days with persistent complains compatible with VITT or thromboembolic event associated with thrombocytopenia. The diagnosis should not be excluded if the rapid anti-PF4 immunological nor chemiluminescence techniques yield negative results. An adapted functional assay should be performed to confirm the diagnosis. Early treatment with intravenous immunoglobulin and non-heparin anticoagulants is essential as delayed diagnosis and administration of appropriate treatment is associated with poor prognosis.

Symptomatic severe acute respiratory syndrome coronavirus 2 reinfection in a lupus patient treated with hydroxychloroquine: a case report.

BACKGROUND: Hydroxychloroquine and chloroquine have been used for hospitalized coronavirus disease 2019 patients because of their antiviral and anti-inflammatory function. However, little research has been published on the impact of the immunomodulatory effect of (hydroxy)chloroquine on humoral immunity. CASE PRESENTATION: We report a case of symptomatic severe acute respiratory syndrome coronavirus 2 reinfection, diagnosed 141 days after the first episode, in a 56-year-old man of Black African origin treated with hydroxychloroquine for lupus erythematosus. No anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies could be detected 127 days after the initial episode of coronavirus disease 2019. CONCLUSIONS: The treatment with hydroxychloroquine probably explains the decreased immune response with negative serology and subsequent reinfection in our patient. As humoral immunity is crucial to fight a severe acute respiratory syndrome coronavirus 2 infection, the use of (hydroxy)chloroquine is likely to have a detrimental effect on the spread of the virus. This case emphasizes that more needs to be learned about the role of antibodies in protecting against severe acute respiratory syndrome coronavirus 2 (re)infection and the role of (hydroxy)chloroquine on humoral immunity.

Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol.

BACKGROUND: Sepsis is a potentially life-threatening condition characterized by a deregulated body's response to infection causing injury to its own tissues and organs. Sepsis is the primary cause of death from infection. If not recognized and treated timely, it can evolve within minutes/hours to septic shock. Sepsis is associated with an acute deficiency of Vitamin C. Despite the proof-of-concept of the benefit of administering Vitamin C in patients with sepsis or septic shock, Vitamin C administration is not yet current practice. OBJECTIVE: To investigate the potential benefit of early administration of high doses of Vitamin C in addition to standard of care in patients with sepsis or septic shock. METHODS: This phase 3b multi-center trial is conducted in 8 hospitals throughout Belgium. In total 300 patients will be randomly assigned to one of two groups in a 1:1 allocation ratio. The intervention group will receive 1.5 g Vitamin C 4 times a day during 4 days, started within 6 hours after admission. The primary outcome is the average post-baseline patient SOFA score. CONCLUSION: This trial will determine whether the early administration of Vitamin C in patients with sepsis or septic shock can lead to a more rapid solution of shock and less deterioration from sepsis to septic shock, hereby reducing morbidity and mortality as well as the length of hospital stay in this patient population. TRIAL REGISTRATION: The C-EASIE trial has been registered on the ClinicalTrials.gov website on 10 February 2021 with registration number NCT04747795. TRIAL SPONSOR: UZ Leuven (sponsor's reference S63213).

Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.

AIMS: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment. METHODS AND RESULTS: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm. CONCLUSIONS: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.

Agreement between Arterial and Capillary pH, pCO2, and Lactate in Patients in the Emergency Department.

BACKGROUND: Blood gas analysis (BGA) is a frequent painful procedure in emergency departments. The primary objective of the study was a quantitative analysis to assess the mean difference and 95% confidence interval of the difference between capillary and arterial BGA for pH, pCO2, and lactate. Secondary objective was to measure the sensitivity and specificity of capillary samples to detect altered pH, hypercarbia, and lactic acidosis. Adults admitted to the ED were screened for inclusion. We studied the agreement between the two methods for pH, pCO2, and lactate with Bland-Altman bias plot analysis and receiver operating characteristic curves. RESULTS: One hundred ninety-seven paired analyses were included. Mean difference for pH between arterial and capillary BGA was 0.0095, and 95% limits of agreement (LOA) were -0.048 to 0.067. For pCO2, mean difference was -0.3 mmHg, and 95% LOA were -8.5 to 7.9 mmHg. Lactate mean difference was -0.93 mmol/L, and 95% LOA were -2.7 to 0.8 mmol/L. At a threshold of 7.34, capillary pH had 98% sensitivity and 97% specificity to detect acidemia; at 45.9 mmHg, capillary pCO2 had 89% sensitivity and 96% specificity to detect hypercarbia. At a threshold of 3.5 mmol/L, capillary lactate had 66% sensitivity to detect lactic acidosis. CONCLUSION: Capillary BGA cannot replace arterial BGA despite high concordance between the two methods for pH and pCO2 and moderate concordance for lactate. Capillary measures had good accuracy when used as a screening tool to detect altered pH and hypercarbia but insufficient sensitivity and specificity when screening for lactic acidosis.

SARS-CoV-2 Diagnostic Tests: Algorithm and Field Evaluation From the Near Patient Testing to the Automated Diagnostic Platform.

Introduction: Since the first wave of COVID-19 in Europe, new diagnostic tools using antigen detection and rapid molecular techniques have been developed. Our objective was to elaborate a diagnostic algorithm combining antigen rapid diagnostic tests, automated antigen dosing and rapid molecular tests and to assess its performance under routine conditions. Methods: An analytical performance evaluation of four antigen rapid tests, one automated antigen dosing and one molecular point-of-care test was performed on samples sent to our laboratory for a SARS-CoV-2 reverse transcription PCR. We then established a diagnostic algorithm by approaching median viral loads in target populations and evaluated the limit of detection of each test using the PCR cycle threshold values. A field performance evaluation including a clinical validation and a user-friendliness assessment was then conducted on the antigen rapid tests in point-of-care settings (general practitioners and emergency rooms) for outpatients who were symptomatic for <7 days. Automated antigen dosing was trialed for the screening of asymptomatic inpatients. Results: Our diagnostic algorithm proposed to test recently symptomatic patients using rapid antigen tests, asymptomatic patients using automated tests, and patients requiring immediate admission using molecular point-of-care tests. Accordingly, the conventional reverse transcription PCR was kept as a second line tool. In this setting, antigen rapid tests yielded an overall sensitivity of 83.3% (not significantly different between the four assays) while the use of automated antigen dosing would have spared 93.5% of asymptomatic inpatient screening PCRs. Conclusion: Using tests not considered the "gold standard" for COVID-19 diagnosis on well-defined target populations allowed for the optimization of their intrinsic performances, widening the scale of our testing arsenal while sparing molecular resources for more seriously ill patients.

Single-tablet regimen of emtricitabine/tenofovir disoproxil fumarate plus cobicistat-boosted elvitegravir increase adherence for HIV postexposure prophylaxis in sexual assault victims.

BACKGROUND: Postexposure prophylaxis (PEP) is a recommended public health intervention after a sexual assault to prevent HIV infection. METHODS: We conducted a retrospective case-control study on how use of a single-tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild) affected adherence to PEP and attendance of a follow-up visit to the STI clinic compared with those who received a multitablet regimen (MTR). Data from sexual assault victims consulting for PEP were prospectively recorded between January 2011 and December 2017. Data were systematically collected on patient demographics, time of medical contact, source risk factors, type of exposure, attendance to follow-up visit, reported completion of PEP and adherence based on pharmacy records. RESULTS: A total of 422 patients received PEP following a sexual assault, of whom 52% had documented completion of a 28-day PEP regimen and 71% attended a follow-up clinic visit. Patients who received an elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF)-based STR had a similar likelihood of attending their first follow-up visit (OR: 0.97; 95% CI: 0.64 to 1.48, p=0.90) but were more likely to complete the PEP regimen (OR: 1.70; 95% CI: 1.16 to 2.50, p=0.007). After adjusting for confounders, those who were prescribed an STR regimen were more likely to complete the PEP regimen (OR: 1.66, 95% CI: 1.09 to 2.53, p=0.019) than those who were prescribed an MTR such as stavudine/lamivudine/lopinavir/ritonavir or zidovudine/lamivudine/indinavir/ritonavir. CONCLUSIONS: Sexual assault victims who were prescribed an STR based on EVG/COBI/FTC/TDF were more likely to complete PEP than those who were prescribed an MTR.